The Effect of Aerobic Exercise on Concussion Recovery: A Pilot Clinical Trial.

OBJECTIVE: The purpose of this study was to pilot safety and tolerability of a 1-week aerobic exercise program during the post-acute phase of concussion (14-25 days post-injury) by examining adherence, symptom response, and key functional outcomes (e.g., cognition, mood, sleep, postural stability, and neurocognitive performance) in young adults. METHOD: A randomized, non-blinded pilot clinical trial was performed to compare the effects of aerobic versus non-aerobic exercise (placebo) in concussion patients. The study enrolled three groups: 1) patients with concussion/mild traumatic brain injury (mTBI) randomized to an aerobic exercise intervention performed daily for 1-week, 2) patients with concussion/mTBI randomized to a non-aerobic (stretching and calisthenics) exercise program performed daily for 1-week, and 3) non-injured, no intervention reference group. RESULTS: Mixed-model analysis of variance results indicated a significant decrease in symptom severity scores from pre- to post-intervention (mean difference = -7.44, 95% CI [-12.37, -2.20]) for both concussion groups. However, the pre- to post-change was not different between groups. Secondary outcomes all showed improvements by post-intervention, but no differences in trajectory between the groups. By three months post-injury, all outcomes in the concussion groups were within ranges of the non-injured reference group. CONCLUSIONS: Results from this study indicate that the feasibility and tolerability of administering aerobic exercise via stationary cycling in the post-acute time frame following post-concussion (14-25 days) period are tentatively favorable. Aerobic exercise does not appear to negatively impact recovery trajectories of neurobehavioral outcomes; however, tolerability may be poorer for patients with high symptom burden.

Temporal lobe epilepsy affects spatial organization of entorhinal cortex connectivity.

Evidence for structural connectivity patterns within the medial temporal lobe derives primarily from postmortem histological studies. In humans and nonhuman primates, the parahippocampal gyrus (PHg) is subdivided into parahippocampal (PHc) and perirhinal (PRc) cortices, which receive input from distinct cortical networks. Likewise, their efferent projections to the entorhinal cortex (ERc) are distinct. The PHc projects primarily to the medial ERc (M-ERc). The PRc projects primarily to the lateral portion of the ERc (L-ERc). Both M-ERc and L-ERc, via the perforant pathway, project to the dentate gyrus and hippocampal (HC) subfields. Until recently, these neural circuits could not be visualized in vivo. Diffusion tensor imaging algorithms have been developed to segment gray matter structures based on probabilistic connectivity patterns. However, these algorithms have not yet been applied to investigate connectivity in the temporal lobe or changes in connectivity architecture related to disease processes. In this study, this segmentation procedure was used to classify ERc gray matter based on PRc, ERc, and HC connectivity patterns in 7 patients with temporal lobe epilepsy (TLE) without hippocampal sclerosis (mean age, 14.86 ±â€¯3.34 years) and 7 healthy controls (mean age, 23.86 ±â€¯2.97 years). Within samples paired t-tests allowed for comparison of ERc connectivity between epileptogenic and contralateral hemispheres. In healthy controls, there were no significant within-group differences in surface area, volume, or cluster number of ERc connectivity-defined regions (CDR). Likewise, in line with histology results, ERc CDR in the control group were well-organized, uniform, and segregated via PRc/PHc afferent and HC efferent connections. Conversely, in TLE, there were significantly more PRc and HC CDR clusters in the epileptogenic than the contralateral hemisphere. The surface area of the PRc CDR was greater, and that of the HC CDRs was smaller, in the epileptogenic hemisphere as well. Further, there was no clear delineation between M-ERc and L-ERc connectivity with PRc, PHc or HC in TLE. These results suggest a breakdown of the spatial organization of PHg-ERc-HC connectivity in TLE. Whether this breakdown is the cause or result of epileptic activity remains an exciting research question.

Broca's area - thalamic connectivity.

Broca's area is crucially involved in language processing. The sub-regions of Broca's area (pars triangularis, pars opercularis) presumably are connected via corticocortical pathways. However, growing evidence suggests that the thalamus may also be involved in language and share some of the linguistic functions supported by Broca's area. Functional connectivity is thought to be achieved via corticothalamic/thalamocortical white matter pathways. Our study investigates structural connectivity between Broca's area and the thalamus, specifically ventral anterior nucleus and pulvinar. We demonstrate that Broca's area shares direct connections with these thalamic nuclei and suggest a local Broca's area-thalamus network potentially involved in linguistic processing. Thalamic connectivity with Broca's area may serve to selectively recruit cortical regions storing multimodal features of lexical items and to bind them together during lexical-semantic processing. In addition, Broca's area-thalamic circuitry may enable cortico-thalamo-cortical information transfer and modulation between BA 44 and 45 during language comprehension and production.

Imaging white matter in human brainstem.

The human brainstem is critical for the control of many life-sustaining functions, such as consciousness, respiration, sleep, and transfer of sensory and motor information between the brain and the spinal cord. Most of our knowledge about structure and organization of white and gray matter within the brainstem is derived from ex vivo dissection and histology studies. However, these methods cannot be applied to study structural architecture in live human participants. Tractography from diffusion-weighted magnetic resonance imaging (MRI) may provide valuable insights about white matter organization within the brainstem in vivo. However, this method presents technical challenges in vivo due to susceptibility artifacts, functionally dense anatomy, as well as pulsatile and respiratory motion. To investigate the limits of MR tractography, we present results from high angular resolution diffusion imaging of an intact excised human brainstem performed at 11.1 T using isotropic resolution of 0.333, 1, and 2 mm, with the latter reflecting resolution currently used clinically. At the highest resolution, the dense fiber architecture of the brainstem is evident, but the definition of structures degrades as resolution decreases. In particular, the inferred corticopontine/corticospinal tracts (CPT/CST), superior (SCP) and middle cerebellar peduncle (MCP), and medial lemniscus (ML) pathways are clearly discernable and follow known anatomical trajectories at the highest spatial resolution. At lower resolutions, the CST/CPT, SCP, and MCP pathways are artificially enlarged due to inclusion of collinear and crossing fibers not inherent to these three pathways. The inferred ML pathways appear smaller at lower resolutions, indicating insufficient spatial information to successfully resolve smaller fiber pathways. Our results suggest that white matter tractography maps derived from the excised brainstem can be used to guide the study of the brainstem architecture using diffusion MRI in vivo.

Broca's area and its striatal and thalamic connections: a diffusion-MRI tractography study.

In the recent decades structural connectivity between Broca's area and the basal ganglia has been postulated in the literature, though no direct evidence of this connectivity has yet been presented. The current study investigates this connectivity using a novel diffusion-weighted imaging (DWI) fiber tracking method in humans in vivo. Our findings suggest direct connections between sub-regions of Broca's area and the anterior one-third of the putamen, as well as the ventral anterior nucleus of the thalamus. Thus, we are the first to provide a detailed account of inferred circuitry involving basal ganglia, thalamus, and Broca's area, which would be a prerequisite to substantiate their support of language processing.

Delayed diagnosis of intracerebral foreign body from the Vietnam War.

We report on a 22-year-old infantryman who sustained a right frontal wound to his head. He was treated and returned to duty immediately. During a computed tomography scan, 38 years after the incident, a metallic foreign body and disruption of the brain consistent with a projectile track were discovered in his brain. In this report, we review similar cases of delayed discovery of unsuspected foreign bodies and the probable nature of the wound.

Diffusion weighted imaging and neuropsychological correlates in adults with mild traumatic brain injury.

Diffusion Tensor Imaging (DTI) is increasingly being used as a research tool in mild Traumatic Brain Injury (mTBI). This article reviews the concepts of diffusion tensor imaging, neuropsychological testing and results to date when applied to mTBI in adults. DTI is being used in conjunction with neuropsychological and electrophysiological measures to provide improved structural/functional correlations of mTBI. Future directions and applications of DTI in mTBI research are suggested.

Lesion characteristics related to treatment improvement in object and action naming for patients with chronic aphasia.

UNLABELLED: Few studies have examined the relationship between degree of lesion in various locations and improvement during treatment in stroke patients with chronic aphasia. The main purpose of this study was to determine whether the degree of lesion in specific brain regions was related to magnitude of improvement over the course of object and action naming treatments. PARTICIPANTS AND METHODS: Fifteen left hemisphere stroke patients with aphasia participated in treatments for object and/or action naming. Two raters assessed extent of lesion in 18 left hemisphere cortical and subcortical regions of interest (ROIs) on CT or MRI scans. Correlations were calculated between composite basal ganglia, anterior cortical, and posterior cortical lesion ratings, on the one hand, and both pretreatment scores and treatment change for both object and action naming, on the other hand. RESULTS: Unexpectedly, greater anterior cortical lesion extent was highly correlated with better object and action naming scores prior to treatment and with greater improvement during treatment when partial correlations controlled for total basal ganglia lesion extent (r ranging from .730 to .858). Greater total basal ganglia lesion extent was highly correlated with worse object and action naming scores prior to treatment and with less improvement during treatment when partial correlations controlled for total anterior lesion extent (r ranging from -.623 to -.785). Correlations between degree of posterior cortical lesion and naming indices generally were not significant. No consistent differences were found between the correlations of ROI lesion ratings with object naming versus action naming scores. CONCLUSION: Large anterior cortical lesions and intactness of the basal ganglia may both contribute to more efficient reorganization of language functions.

Effects of donepezil on verbal memory after semantic processing in healthy older adults.

OBJECTIVE: To learn if acetylcholinesterase inhibitors alter verbal recall by improving semantic encoding in a double-blind randomized placebo-controlled trial. BACKGROUND: Cholinergic supplementation has been shown to improve delayed recall in adults with Alzheimer disease. With functional magnetic resonance imaging, elderly adults, when compared with younger participants, have reduced cortical activation with semantic processing. There have been no studies investigating the effects of cholinergic supplementation on semantic encoding in healthy elderly adults. METHOD: Twenty elderly participants (mean age 71.5, SD+/-5.2) were recruited. All underwent memory testing before and after receiving donepezil (5 mg, n=11 or 10 mg, n=1) or placebo (n=8) for 6 weeks. Memory was tested using a Levels of Processing task, where a series of words are presented serially. Subjects were either asked to count consonants in a word (superficially process) or decide if the word was "pleasant" or "unpleasant" (semantically process). RESULTS: After 6 weeks of donepezil or placebo treatment, immediate and delayed recall of superficially and semantically processed words was compared with baseline performance. Immediate and delayed recall of superficially processed words did not show significant changes in either treatment group. With semantic processing, both immediate and delayed recall performance improved in the donepezil group. CONCLUSIONS: Our results suggest that when using semantic encoding, older normal subjects may be aided by anticholinesterase treatment. However, this treatment does not improve recall of superficially encoded words.

Spatial attentional bias in normal people: object or viewer-centered.

When bisecting radial lines, normal subjects often have a distal bias. To help in explaining this systematic bias, it has been proposed that normal people have an attentional bias to the top of the lines (object centered hypothesis) or toward stimuli falling in the lower portion of the retina (retinotopic hypotheses) or to distal peripersonal space (body centered hypotheses). The primary aim of this study is to test these hypotheses by having normal subjects bisect radial lines, placed in a clockwise distribution in the transverse plane, below eye level. Our results demonstrate that the perception of the midpoint progressively changes as a function of the body centered orientation of the lines, with subjects demonstrating a progressively greater distal bias as they approached the midsagittal plane or radial condition. These findings provide support for the postulate that distal bias on radial lines bisections is body centered.

Spreading activation of lexical-semantic networks in Parkinson's disease.

Although dopamine may act as a neuromodulator of spreading activation within semantic networks, this role of dopamine in lexical networks has not been investigated. Hence, we sought to investigate the effects of Parkinson's disease (PD), which is associated with dopamine depletion, on spreading activation in the lexical networks. Ten Parkinson's disease patients and 11 normal controls performed the controlled oral word association test and the average word frequency for their responses was calculated and used as an index of spreading activation. The PD patients exhibited a lower average word frequency, suggesting increased spreading activation, and a significant relationship between the strength of the initial activation and subsequent extent of spreading activation. Most patients were taking dopaminergic medication and future studies may benefit from examining the changes in spreading activation in lexical networks in PD patients on versus off medication or in healthy controls taking either a placebo or a dopaminergic medication. Although these alterations in lexical access might be related to the reduction of dopamine, one of the hallmarks of PD, these patients also have alterations of other neurotransmitter systems and further studies are needed to more clearly identify the role played by these neurotransmitter on lexical access.

Carbidopa/levodopa-responsive myoclonus.

A 64-year-old right-handed woman's right hand and arm developed spontaneous jerks that eventually involved her trunk. As she had some features of parkinsonism, she was treated with carbidopa/levodopa and her myoclonus dramatically improved. The mechanism accounting for this improvement is unknown.

Asymmetrical alien hands in corticobasal degeneration.

There are several forms of alien limb, but alien limb in corticobasal degeneration (CBD) is not well understood. We studied a patient with CBD who demonstrated two different types of alien limb. With his right hand he demonstrated a tactile avoidance response with levitation. With his left hand, he demonstrated continuous tactile pursuit of the examiner's hand ("tactile mitgehen"). Mitgehen is often associated with frontal dysfunction, but avoidance response and levitation are often associated with parietal dysfunction.

Ipsilesional attentional-approach neglect or crossover effect.

Patients with ipsilateral neglect (IN) bisect lines toward contralesional space. It has been posited that IN might be induced by an attempt at compensation, as part of the crossover effect, where patients with an ipsilesional bias when bisecting long lines, cross over and develop a contralesional bias on short lines or as a release of an approach (grasp) behavior that might be attentional or intentional. To test these alternative hypotheses we had a patient with IN from a right medial frontal lesion bisect lines that contained no cue, a left-sided cue, a right-sided cue, and bilateral cues. If this patient had ipsilateral neglect (IN) because of a crossover effect or compensation, right-sided cues should have influenced bisection more than left-sided cues. We, however, found that only left-sided cues induced a significant change (left-sided deviation) providing support for the attentional-approach (grasp) hypothesis. Further support of this contralesional attentional grasp hypothesis comes from the observation that this patient also had ipsilesional extinction to simultaneous stimuli.